Thymidylate synthase (TYMS) tandem repeat polymorphism: As a predictive genetic marker for the risk of Alzheimer's disease

Abstract

Moderately elevated plasma homocysteine level is associated with an increased risk of Alzheimer's disease. Thymidylate synthase (TYMS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are involved in the homocysteine metabolic pathway. In this study, we tried to find the association between TYMS tandem repeat polymorphism and Alzheimer's disease. We analyzed the genotype of the TYMS and MTHFR C677T polymorphisms in 68 Alzheimer's patients and 413 healthy controls. The mean plasma homocysteine level was higher in Alzheimer's disease patients than in healthy controls (p < 0.05). Those subjects who carried at least one TYMS 2R allele [2R(+)] showed an increased risk of Alzheimer's disease (AOR, 2.09; 95%CI, 121-425). However, the MTHFR C677T polymorphism was not associated with an increased risk of Alzheimer's disease. In the comparison of the combinations of polymorphisms, the risk of Alzheimer's disease was highest in the subjects with the [2R(+)/T(+)] combined genotypes (AOR, 2.76; 95%CI, 130-6.71). In conclusion, particular genotype of TYMS tandem repeat polymorphism and combined genotypes of the TYMS tandem repeat and MTHFR C677T polymorphisms appeared to be predictive genetic biomarkers for the risk of Alzheimer's disease. © The Genetics Society of Korea.